GM00712

GM00712 Fibroblast from Spleen, Keloid

Description:

THANATOPHORIC DYSPLASIA; TD
FIBROBLAST GROWTH FACTOR RECEPTOR 3; FGFR3

Affected:

Yes

Sex:

Male

Age:

1 DA (At Sampling)

Overview

Repository

NIGMS Human Genetic Cell Repository

Subcollection

Heritable Diseases

Class

Disorders of Connective Tissue, Muscle, and Bone

Biopsy Source

Keloid

Cell Type

Fibroblast

Tissue Type

Spleen

Transformant

Untransformed

Sample Source

Fibroblast from Spleen, Keloid

Race

White

Family Member

Relation to Proband

proband

Confirmation

Clinical summary/Case history

Species

Homo sapiens

Common Name

Human

Remarks

Fibroblast culture (spleen); same pt as GM00711; donor subject has a C>T transition at nucleotide 742 in exon 6 of the FGFR3 gene (742C>T) resulting in a substitution of cysteine for arginine at codon 248 [Arg248Cys (R248C)]

Characterizations

Passage Frozen

IDENTIFICATION OF SPECIES OF ORIGIN

Species of Origin Confirmed by Nucleoside Phosphorylase Isoenzyme Electrophoresis

MUTATION VERIFICATION

The gene mutation listed for this cell line was confirmed by sequencing and FRET probe analysis on a fibroblast line GM00714 from this same donor.

Gene

FGFR3

Chromosomal Location

4p16.3

Allelic Variant 1

134934.0005; THANATOPHORIC DYSPLASIA, TYPE I; TD1

Identified Mutation

ARG248CYS; Of 39 individuals with type I thanatophoric dysplasia (187600), Tavormina et al. (1995) found an arg248-to-cys mutation in 22 and a ser371-to-cys mutation (134934.0006) in 1. Both of these mutations were in the extracellular region of the protein. Amino acid substitution resulted from a C-to-T transition at nucleotide 742. Although type II thanatophoric dysplasia cases have been found to have a single recurrent K650E change (134934.0004), type I cases have different mutations affecting either the extracellular or intracellular domains of FGFR3. However, mutations in the FGFR3 gene were identified in only approximately 60% of the type I TD cases. These findings, and the range of symptoms observed, suggested that type I TD is heterogeneous in genetic background. Pokharel et al. (1996) described a Japanese type I TD patient followed for more than 9 years. They found that the patient had the arg248-to-cys mutation as did 4 other Japanese cases of type I TD. No association was found with the ser371-to-cys mutation.